Systems and methods for controlling reperfusion in a vessel

ABSTRACT

A system for controlling reperfusion in a blood vessel of a patient including a flexible elongated member configured and dimensioned for insertion in the vessel of the patient, the elongated member having a proximal portion and a distal portion, the elongated member configured for insertion so the distal portion extends distal of a clot in the blood vessel. A sensor is positioned at the distal portion of the elongated member for positioning distal of the blood clot, the sensor measuring a parameter of blood downstream of the clot. An indicator communicates with the sensor, the indicator indicating a measured parameter for insertion of an instrument for controlling blood flow.

This application claims priority from provisional application62/276,702, filed Jan. 8, 2016, the entire contents of which areincorporated herein by reference.

BACKGROUND

Technical Field

This application relates to a system and method for controllingreperfusion in a vessel.

Background of Related Art

Cerebrovascular disease refers to diseases of the brain caused byvascular abnormalities which result in abnormal cerebral blood flow. Themost common cause of cerebrovascular disease is narrowing of the majorarteries supplying blood to the brain, resulting in thrombogenic diseaseor sudden occlusion of blood flow, which if large enough results inischemic stroke.

Clots (Ischemic Stroke) can originate in various areas and be caused bydifferent modalities. These different modalities create clots that varyin consistency. The clot can be platelet rich (runny) or fibrin rich(hard) or anywhere in between the two. Ischemic stroke is caused by thethrombosis of a major vessel supplying blood to a region of the brain. Ashortage of blood in the cerebral tissue leads to the deletion ofmetabolites such as oxygen and glucose, which in turn causes depletionof energy stores of the cells. Therefore, it is critical to remove theclots to restore adequate blood supply to the brain.

Current treatments for clot removal include application of thrombolyticdrugs to dissolve the clot and mechanical thrombectomy devices inminimally invasive procedures. A problem encountered with theseapproaches is that the composition of the clot is undetectable in situ,while the efficacy of these approaches is dependent in part on the clotcomposition. Therefore, the physician is taking one of the knownapproaches for treatment of the clot without the knowledge of the clotmakeup, e.g., its consistency. This can lead to inconsistent results aswell as failure to properly treat the clot.

It would therefore be beneficial if the surgeon could identify the typeof clot beforehand to better assess how the clot could be treated. Suchprior knowledge would greatly enhance clot removal as the surgeon canadapt the approach to better match the treatment device or drugs withthe type of clot.

In addition, in cerebrovascular disease, the vitality of the vasculaturedistal to the clot is compromised once the clot lodges in place.Vasculature that has been deprived of oxygenated blood will necrose andbecome friable. Once blood flow is restored after clot removal, suchblood flow could potentially cause a hemorrhagic event, which means thevessel can bleed out and burst open. Currently, surgeons do not haveadequate knowledge of the vasculature downstream of the clot andtherefore cannot accurately assess the risk of clot removal bydissolution or mechanical thrombectomy.

It would be beneficial if the surgeon could determine the health of thevasculature distal to the clot prior to removal of the clot so thesurgeon could determine if clot removal is advisable and/or takenecessary precautions during clot removal so the vessels are notcompromised. Prior attempts to measure pH using magnetic resonanceimaging (MRI) technique have been attempted, as explained for example in“Modelling of pH Dynamics in Brain Cells After Stroke”, by PiotrOrlowski, et al., published in Interface Focus, The Royal Society, 2011.However, these attempts to date have been unsuccessful. Additionally,relying on MRI is very expensive and requires relatively complexmathematical models. Further, an ischemic event might need to be treatedin an ambulance prior to arrival at a hospital and thus an MRI is notpossible. Therefore, although the role of pH is recognized, the needexists to utilize this parameter to readily and inexpensively determinein hospital and non-hospital settings vascular tissue health to enhanceblood clot removal or prevent clot removal where the risk is too great.This would provide great benefits not only for hospital treatment butfor pre-hospital treatment such as in the ambulance or home prior toarrival at the hospital.

Additionally, after assessment of the health of the vasculature and aselection of the proper clot treatment, it might be beneficial tocontrol the restoration of blood flow. Being able to determine thehealth of the vasculature would thus advantageously enable gradualreturn of blood flow if deemed necessary to reduce the risk ofhemorrhaging.

SUMMARY OF THE INVENTION

The present invention provides a system for determining and/orcontrolling the rate of blood flow. The system can be used with a systemand method for assessing vasculature downstream of the clot and/or asystem and method for assessing the blood clot, the two systems usableindependently, or alternatively, usable together as either separatesystems or a single (combined) system. The system of assessingvasculature downstream of the clot enables a) selection of the best clottreatment method, which can include non-removal of the clot, and/or b)selection of the desirable rate of return of blood flow after removal ofthe blood clot.

In one aspect, the present invention provides a system for determining apH level of blood in a vessel of a patient. The system comprises aflexible elongated member configured and dimensioned for insertion inthe vessel of the patient, the elongated member having a proximalportion and a distal portion and configured for insertion so the distalportion extends past a blood clot for positioning of the distal portiondistal of the blood clot. A sensor is positioned at the distal portionof the elongated member for positioning distal of the blood clot. Aconnector connects the elongated member to an indicator, the sensormeasuring the pH level of blood, preferably in a closed or asubstantially closed system downstream of the blood clot, to therebydetermine pH of the vessel downstream of the blood clot to determine thecondition of the vessel to assess subsequent treatment or non-treatmentof the blood clot. The indicator provides an indication of the blood pHmeasured by the sensor.

In one embodiment, the flexible elongated member comprises a catheter.In another embodiment, the flexible elongated member comprises aguidewire.

In one embodiment, the sensor is embedded in a wall of the elongatedmember. In another embodiment, the sensor is positioned on an outersurface of the elongated member.

The system can include in some embodiments a second sensor for sensing aparameter of the blood clot and a second indicator to indicate thesensed parameter, the second sensor connected to the second indicator.In some embodiments, the second sensor senses a density of the bloodclot. In some embodiments, the second sensor is positioned on a secondelongated member coaxial with the elongated member carrying the sensorfor measuring pH. In some embodiments, the second sensor is proximal ofthe first sensor.

In accordance with another aspect, the present invention provides amethod for determining a pH level of blood downstream of a blood clot ina vessel of a patient comprising the steps of:

-   -   providing an elongated flexible member;    -   inserting the flexible member through vasculature of the patient        and past the blood clot to a position downstream of the blood        clot in the vessel;    -   sensing a pH level of the blood downstream of the clot; and    -   indicating to the user the pH level of the blood to enable the        user to determine a pH level of the vessel downstream of the        blood clot for subsequent selection of a clot treatment        approach.

In some embodiments, the method further comprises the step ofdetermining a density of the blood clot to determine a clot treatmentmethod. In some embodiments, the step of determining the density of theblood clot utilizes a sensor proximal of a sensor used for sensing pH ofthe blood. In some embodiments, one of the density sensor and pH sensoris on a first elongated flexible member and the other sensor is on asecond elongated flexible member coaxial with the first elongatedmember.

In accordance with another aspect, the present invention provides asystem for determining an oxygen level of blood in a vessel of apatient. The system comprises a flexible elongated member configured anddimensioned for insertion in the vessel of the patient, the elongatedmember having a proximal portion and a distal portion and configured forinsertion so the distal portion extends past a blood clot forpositioning of the distal portion distal of the blood clot. A sensor ispositioned at the distal portion of the elongated member for positioningdistal of the blood clot. A connector connects the elongated member toan indicator, the sensor measuring the oxygen level of blood, preferablyin a closed or a substantially closed system downstream of the bloodclot, to thereby determine the oxygen level of the vessel downstream ofthe blood clot to determine the condition of the vessel to assesssubsequent treatment of the blood clot. The indicator provides anindication of the oxygen level of the blood measured by the sensor.

In accordance with another aspect, the present invention provides amethod for determining an oxygen level of blood downstream of a bloodclot in a vessel of a patient comprising the steps of:

-   -   providing an elongated flexible member;    -   inserting the flexible member through vasculature of the patient        and past the blood clot to a position downstream of the blood        clot in the vessel;    -   sensing an oxygen level of the blood downstream of the clot; and    -   indicating to the user the oxygen level of the blood to enable        the user to determine an oxygen level of the vessel downstream        of the blood clot for subsequent selection of a clot treatment        approach.

In accordance with another aspect of the present invention, a system fordetermining a density of a blood clot in a vessel of a patient forsubsequent selection of a treatment method is provided. The systemcomprises a flexible elongated member configured and dimensioned forinsertion in the vessel of the patient, the elongated member having aproximal portion and a distal portion and the distal portion configuredfor insertion adjacent the blood clot. A sensor is positioned at thedistal portion of the elongated member. A connector connects theelongated member to an indicator, the sensor determining the density ofthe blood clot and the indicator providing an indication of thedetermined density.

In one embodiment, the flexible elongated member comprises a catheter.In another embodiment, the flexible elongated member comprises aguidewire.

The system in some embodiments further comprises a transmitter at thedistal portion of the elongated member for transmitting ultrasonic wavestoward the blood clot, and the density of the blood clot is determinedby ultrasonic wave feedback. The system in some embodiments can furtherinclude a pH sensor for measuring pH of blood downstream of the clot andan indicator for indicating measured pH.

The present invention provides in another aspect a method fordetermining a density of a blood clot in a vessel of a patient forsubsequent selection of a clot treatment method. The method comprises:

-   -   providing a flexible elongated member configured and dimensioned        for insertion in the vessel of the patient, the elongated member        having a proximal portion and a distal portion, the elongated        member distal portion configured for insertion adjacent a blood        clot;    -   transmitting ultrasonic waves toward the blood clot; and    -   determining the density of the blood clot based on the        ultrasonic wave feedback.

In some embodiments, the method further provides a visual indication ofthe determined density.

In some embodiments, the method further includes positioning theelongated member so that a distal tip extends past the blood clot and adensity sensor is positioned proximal of the distal tip within the bloodclot.

In accordance with another aspect, the present invention provides asystem for determining treatment after determining a pH level of bloodin a vessel of a patient comprising a flexible elongated memberconfigured and dimensioned for insertion in the vessel of the patient,the elongated member having a proximal portion and a distal portion andconfigured for insertion so the distal portion extends distal of a bloodclot. A pH sensor is positioned at the distal portion of the elongatedmember for positioning distal of the blood clot and an indicatorcommunicates with the sensor to indicate to a user a measured pH level.The sensor measures the pH level of the blood downstream of the bloodclot to determine the condition of the vessel to assess a) treatment ofthe blood clot in response to the pH level indicated by the indicator;and b) desired blood flow rate during and/or after blood clot removal.

In some embodiments, if the pH level exceeds a predetermined level,blood flow rate is reduced post blood clot removal.

The system may further include a connector connecting the elongatedmember to the indicator. In some embodiments, the flexible elongatedmember comprises a guidewire; in other embodiments, the flexibleelongated member comprises a catheter.

In some embodiments the sensor is embedded in a wall of the elongatedmember; in other embodiments, the sensor is positioned on an outersurface of the elongated member.

The system can further include a catheter positionable over the flexiblemember. In some embodiments, the catheter has a mechanical device formechanically removing the blood clot and a balloon distal of themechanical device inflatable to reduce blood flow. In other embodiments,the catheter has a lumen to transport cryogenic fluid distal of theblood clot to reduce blood flow.

In accordance with another aspect of the present invention a method fordetermining a blood clot treatment in response to assessing a pH levelof blood downstream of the blood clot in a vessel of a patient isprovided comprising the steps of:

-   -   providing an elongated flexible member;    -   inserting the flexible member through vasculature of the patient        and past the blood clot to a position downstream of the blood        clot in the vessel;    -   measuring a pH level of the blood downstream of the blood clot;        and    -   indicating to the user the pH level of the blood to enable the        user to determine a pH level of the vessel downstream of the        blood clot for a) selection of non-treatment or a treatment        method to remove the blood clot and b) if treatment is selected,        a determination whether slow reperfusion during and/or after        removal of the blood clot is warranted.

In some embodiments, a pH sensor on a distal portion of the flexiblemember performs the step of measuring a pH level. In some embodiments,the method further comprises the step of inflating a balloon prior to orafter removal of the blot clot to slow reperfusion if a determination ismade that slow perfusion is warranted. In other embodiments, the methodfurther comprises the step of delivering a cryogenic fluid prior to orafter removal of the blood clot to slow reperfusion if a determinationis made that slow perfusion is warranted.

In some embodiments, the step of inflating the balloon is performed ifthe indicator indicates the pH level is below 7, although other levelsare also contemplated. In some embodiments, if the indicator shows thepH below a predetermined level, the slow perfusion after removal of theblood clot is warranted. In some embodiments, the step of delivering acryogenic fluid is performed if the indicator indicates the pH level isbelow 7, although other levels are also contemplated.

In some embodiments, the flexible member is a guidewire, and the methodfurther includes the step of inserting a catheter over the guidewire,the catheter having structure to enable slow perfusion of blood afterremoval of the blood clot.

In accordance with another aspect of the present invention, a system forassessing a condition of an organ by measuring a pH level of bloodwithin vasculature of the organ is provided comprising a flexibleelongated member configured and dimensioned for insertion in thevasculature of the organ. The elongated member has a proximal portionand a distal portion and is configured for insertion so the distalportion extends into the vasculature of the organ. A pH sensor ispositioned at the distal portion of the elongated member for positioningwithin the vasculature, and an indicator communicates with the sensor,the indicator indicating a measured pH level. The pH sensor measures thepH level of the blood within the vasculature of the organ to assess thecondition of the organ.

In accordance with another aspect of the present disclosure, a methodfor regulating reperfusion of blood flow is provided comprising thesteps of:

-   -   a) inserting the elongated flexible member through vasculature        of the patient to a position downstream of the blood clot in the        vessel, the elongated flexible member having a sensor to measure        pH level of the blood downstream of the blood clot;    -   b) measuring pH level of the blood downstream of the blood clot;    -   c) either before or after step (b), inserting the catheter over        the elongated flexible member;    -   d) providing an indicator to a clinician of the measured pH        level;    -   e) removing the blood clot if the pH level is below a first        predetermined level; and    -   f) if the pH level is below the first predetermined level,        slowing the rate of perfusion of the blood after removal of the        blood clot if the pH level does not exceed a second        predetermined level.

In some embodiments, the first predetermined level is the same as thesecond predetermined level; in other embodiments, the firstpredetermined level is different, i.e., less, than the secondpredetermined level.

In some embodiments, the step of slowing perfusion after removal of theblood clot comprises the step of adjusting inflation of an inflatableballoon carried by the catheter. In other embodiments, the step ofslowing perfusion after removal of the blood clot comprises the step ofinjecting a cryogenic fluid through the catheter.

In accordance with another aspect of the present invention, a system forcontrolling reperfusion in a blood vessel of a patient is providedcomprising a flexible elongated member configured and dimensioned forinsertion in the vessel of the patient, the elongated member having aproximal portion and a distal portion and configured for insertion sothe distal portion extends distal of a clot in the blood vessel. Asensor is positioned at the distal portion of the elongated member forpositioning distal of the blood clot, the sensor measuring a parameterof blood downstream of the clot. An indicator communicates with thesensor, the indicator indicating a measured parameter for insertion ofan instrument for controlling blood flow.

In some embodiments, a catheter is positionable over the flexiblemember, the catheter having a mechanical device for mechanicallyremoving the blood clot and a balloon distal of the mechanical device,the balloon inflatable to reduce blood flow. In other embodiments, acatheter is positionable over the flexible member, the catheter having alumen to transport cryogenic fluid distal of the blood clot to reduceblood flow. In some embodiments, the parameter is a pH level of blood,and the sensor is a pH sensor measuring the pH level of the blooddownstream of the blood clot to determine the condition of the vessel,and if the pH level is less than a predetermined level, blood flow rateis reduced after blood clot removal. In other embodiments, the parameteris an oxygen level of blood, and the sensor is an oxygen sensormeasuring the oxygen level of the blood downstream of the blood clot todetermine the condition of the vessel, and if the oxygen level is lessthan a predetermined level, blood flow rate is reduced after blood clotremoval.

In accordance with another aspect of the present invention, a system fordetermining the rate of reperfusion in a vessel after removal of a bloodclot is provided which includes means for measuring pH of blooddownstream of a blood clot, means for indicating the measured pH, meansfor removing the blood clot and means for controlling the rate of bloodflow after clot removal. In some embodiments, the controlling meansincludes an inflatable balloon; in other embodiments the controllingmeans includes providing cryogenic fluid. In some embodiments, theremoving means includes a mechanical thrombectomy device.

In accordance with another aspect of the present invention, a method fordetermining the rate for reperfusion in a vessel of a patient isprovided comprising the steps of providing an elongated flexible member,inserting the flexible member through vasculature of the patient andpast a clot in the vessel to a position downstream of the clot in thevessel, measuring a parameter of the blood downstream of the blood clotand indicating to the user the parameter of the blood to enable the userto determine a condition of the vasculature and determine a rate ofreperfusion. In some embodiments, a pH sensor is on a distal portion ofthe flexible member for measuring a pH level. The method may furthercomprise the step of inflating a balloon prior to removal of the blotclot to slow reperfusion if a determination is made that slow perfusionis warranted. The method may alternatively comprise the step ofdelivering a cryogenic fluid prior to removal of the blood clot to slowreperfusion if a determination is made that slow perfusion is warranted.

The method may further comprise the step of slowing perfusion afterremoval of the blood clot by adjusting inflation of an inflatableballoon carried by the catheter.

The method may, further comprise the step of slowing perfusion afterremoval of the blood clot by injecting a cryogenic fluid through thecatheter.

BRIEF DESCRIPTION OF THE DRAWINGS

Preferred embodiments of the present disclosure are described hereinwith reference to the drawings wherein:

FIG. 1 is a side view of a first embodiment of the system of the presentinvention illustrating a catheter coupled to a pH reader and showing thecatheter tip positioned distal of the blood clot;

FIG. 2A is a close up perspective view of the pH reader of FIG. 1;

FIG. 2B is a close up perspective view of an oxygen level reader;

FIG. 3A is a close up view of the catheter tip of FIG. 1 showing the pHsensor on an outer surface of the catheter for determining blood pH;

FIG. 3B is a close up view of the catheter tip showing the pH sensorembedded in the wall of the catheter in accordance with an alternateembodiment;

FIG. 4 is a close up perspective of the coupler of FIG. 1 for connectingthe pH reader cable to the catheter;

FIG. 5 is a close up view of the vasculature illustrating the cathetertip of FIG. 1 positioned past a blood clot;

FIG. 6 is a side view of an alternate embodiment of the system of thepresent invention illustrating a guidewire coupled to a pH reader andshowing the guidewire positioned distal of the blood clot;

FIG. 7 is a close up perspective view of the coupler connecting the pHreader cable to the guidewire;

FIG. 8A is a close up view of the guidewire of FIG. 6 positioned distalof the clot and showing the pH sensor on the outer tip of the guidewire;

FIG. 8B is a cutaway view showing the pH sensor embedded in the wall ofthe guidewire in accordance with an alternate embodiment;

FIG. 8C is a close up view of an alternate embodiment having a densitysensor spaced from the distal tip;

FIG. 9A is side view of an alternate system of the present inventionillustrating a catheter coupled to a density reader and showing thecatheter tip positioned distal of the blood clot;

FIG. 9B is a close up view of the distal portion of the catheter of FIG.9A showing the density sensor within the clot;

FIG. 10 is a close up view of the density reader of FIG. 9A showing aclot density reading;

FIG. 11A is a side view of an alternate embodiment of the system of thepresent invention illustrating a guidewire coupled to a density readerand showing the guidewire positioned distal of the blood clot;

FIG. 11B is a close up view of the distal portion of the guidewire ofFIG. 11A, with the clot broken away to show the density sensor withinthe clot;

FIG. 12A is a side view of another alternate system of the presentinvention showing a catheter coupled to a pH reader and a guidewirecoupled to a density reader, and further showing the catheter tip andguidewire positioned distal of the blood clot;

FIG. 12B is a close up view of the distal end of the catheter andguidewire of FIG. 12A, showing retraction of the catheter to expose thedensity sensor on the guidewire;

FIG. 13 is an enlarged view of the density reader of FIG. 12A;

FIG. 14A is a front view illustrating the introducer sheath positionedin the femoral artery and the guide catheter shown advanced into thecerebral artery;

FIG. 14B is a front view similar to FIG. 14A showing the guidewire ofthe present invention advanced through the guide catheter and past thecerebral blood clot;

FIG. 14C is a front view similar to FIG. 14B showing a microcatheter fortreating the blood clot advanced over the guidewire, and further showingthe balloon of the microcatheter inflated to cause slow reperfusion asthe blood clot is removed;

FIG. 14D is a front view similar to FIG. 14C showing an alternateembodiment of a microcatheter for treating the blood clot advanced overthe guidewire, and further showing the injection of cryogenic fluid toenable slow reperfusion as the blood clot is removed;

FIG. 14E is a front view similar to FIG. 14C showing an alternateembodiment of a microcatheter for treating the blood clot advanced overthe guidewire, and further showing the balloon of the microcatheterinflated as the blood clot is removed; and

FIG. 14F is a front view similar to FIG. 14E showing an alternateembodiment with a balloon on the guide catheter.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

The present invention provides a system for determining the health orcondition of the vasculature distal of the blood clot. This aids theclinician in assessing the effect of removal of the blood clot from thevessel. This can also enable the clinician to assess the rate ofreperfusion desirable post clot treatment. The present invention alsoprovides a system for determining the type of blood clot. This enablesthe clinician to assess the best mode of treatment of the blood clot.These two systems can be used independently or alternatively can be usedtogether. That is, it is contemplated that only one of the systems isutilized so the user measures only one of the parameters, i.e., eitherhealth of vasculature or type of clot. However, it is also contemplatedthat both systems be utilized so the user can determine both parameters.These systems are described in detail below.

Note in reference below to the drawings, like reference numeralsidentify similar or like components throughout the several views.

Vasculature Determination

Turning first to the system for determining the health or condition ofthe vasculature, this system is illustrated in FIGS. 1-8, with FIGS. 1-5illustrating an embodiment where the pH sensor is located on a catheterand FIGS. 6-8B illustrating an embodiment where the pH sensor is locatedon a guidewire. It is also contemplated that a pH sensor can bepositioned on the catheter and on the guidewire, and it is alsocontemplated that one or more pH sensors can be positioned on thecatheter and one or more pH sensors can be positioned on the guidewire.Multiple sensors would enable different regions of the blood (andtherefore the vasculature) to be measured. In certain embodimentsutilizing multiple pH sensors, the sensors can be spaced apartsufficiently so that a pH measurement can be taken both upstream anddownstream of the blood clot for comparative purposes in assessingvasculature health.

The system for measuring pH is beneficial since in certain instances,the vitality of the vasculature distal to the blood clot is compromisedonce the clot lodges in place. Vasculature that has been deprived ofoxygenated blood will necrose and become friable. Once blood flow isrestored after clot removal, such blood flow could potentially cause ahemorrhagic event, which means the vessel can bleed out and burst open.Therefore, this system provides a way of determining the health of thevasculature distal to the clot so the physician could determine if clotremoval is advisable, determine the best method to remove the clot ortake other precautions during clot removal. That is, the physician willbe able to determine if the clot should be removed based upon the pHcontent of the vasculature distal to the clot, and if removal isdesirable, assess the best way to restore blood flow as the clot isremoved.

Such determination can be done measuring pH of the blood. It could alsobe accomplished in an alternate embodiment by sensing oxygen levels inthe blood which would provide an indication of the health of thevasculature. Other parameters could also be measured.

With respect to pH, it is understood that intracellular pH is importantin the maintenance of normal cell function. Blood pH is regulated by asystem of buffers that continuously maintain its normal range of 7.35 to7.45. Blood pH drop below 7 or above 7.45 can cause serious problems,including death. Studies have shown that carbon dioxide plays a vitalrole in blood pH abnormality. Carbon dioxide serves as a buffer. Ascarbon dioxide becomes depleted, the pH drops and acidosis and/orapoptosis occurs.

With the presence of a blood clot, there is essentially a closed system(or substantially closed system) created in the vasculature since bloodflow downstream of the clot has mostly stopped. Being a closed system,the pH of the blood can be measured and the blood pH will be indicativeof the pH of the adjacent vasculature. Thus, the measurement of theblood pH as described herein provides an inexpensive, accurate andeffective way to determine the pH and thus the health of the adjacentvasculature. The pH can be measured utilizing known techniques such asan ionic potential sensor that converts the activity of a specific iondissolved in a solution into an electric potential which can bemeasured. Known glass and crystalline membranes can be utilized.

It is also contemplated that instead of measuring blood pH, the oxygenlevel of the blood can be measured downstream of the blood clot,preferably in a closed or substantially closed system, to therebydetermine the health of the vasculature.

The system of the present invention provides a quick and simpleeffective measurement of the blood downstream of the clot and enables adetermination of blood clot treatment either during or prior tohospitalization, such as in the ambulance ride, wherein the treatmentmethod can be determined so as to prevent cerebral hemorrhaging. This isaccomplished without expensive and cumbersome equipment such as MRImachines

The system not only enables determination of the optimized treatment ofthe blood clot but in cases where it determines blood clot removal isindicated, it enables control of reperfusion. That is, based on the pHmeasurement, it provides an indication whether restoration of normalblood flow as a result of clot removal is acceptable, i.e., whether thevessel is in condition to handle restoration of normal blood flow, orwhether restoration of blood flow needs to be controlled, i.e., delayedand/or restored slowly until the pH level rises to an acceptable level.

Several ways to control reperfusion are discussed below by way ofexample. Note that the system for measuring pH can be utilized prior to,during and after blood clot treatment to provide indications of pHlevels of the blood and thus the vasculature at various times.

Turning more specifically to the system of FIGS. 1-5, catheter 10 has aproximal portion 12 and a distal portion 14. The catheter tube 16 issufficiently flexible to navigate the small vessels while having somerigidity to enable it to be directed around the curves of thevasculature. An RHV (rotating hemostatic valve) 20 is attached to thecatheter hub 22 and includes a side arm 24 for fluid injection and/oraspiration. Coupler (connector) 30 is attached to the catheter 10, andis connected to cable 34 which is connected to pH reader (meter) 40. Inone embodiment, as shown in FIG. 4, the coupler 30 is u-shaped withopening 31 between the legs of the “u” dimensioned to frictionally clamponto the outer wall of the catheter 10. That is, the coupler 30 is shownin the embodiment of FIG. 1 in the form of a U-shaped clip with theradius of the U smaller than that of the outer wall of the catheter soit flexes outwardly when placed over the strain relief of the catheterand then is frictionally retained on the catheter. In anotherembodiment, a second connector (coupler) half is placed opposite theconnector to form a 360 degree clip or clamp surrounding the outer wallof the catheter to retain the connector on the catheter 10. Othermethods of attachment are also contemplated such as magneticattachments. Cable 34 is connected to the coupler at one end 35 andconnected at the opposing end 36 to reader 40. As shown (FIG. 1), thecoupler 30 is attached to the region of catheter 10 just distal of hub22, although other locations are also contemplated. The coupler 30 canbe attached to the strain relief of the catheter 10 to enhance coupling.

The pH sensor 26 for measuring blood pH is positioned at the distalportion 14 of the catheter 10 and is electrically coupled to cable 34via a pair of wires (not shown) extending from the sensor 26 to thecoupler 30 and/or cable 34. The wires can be embedded in a wall of thecatheter 10 or alternatively extend through a lumen in the catheter 10.In the embodiment of FIG. 3A the sensor 26 is positioned on an outerwall of the catheter 10, extending circumferentially around 360 degrees.The sensor can also be incorporated into a marker band at the tip of thecatheter 10. In the alternate embodiment of FIG. 3B, the sensor 26′ ispositioned inside the catheter 10, either internal of the inner catheterwall or alternatively embedded in the wall of the catheter 10′. Wires 27connect the sensor 26′ to the conductor 30 and/or cable 24, with twolines coming into the reader 40 with two lines extending to the sensor26.

The pH reader 40 provides an indicator device and contains an on offswitch 42. A reading 44 provides a visual indication, as a numericvalue, of the measured pH of the blood to inform the user of the pH ofthe blood, and therefore the vasculature. FIG. 2 shows by way of examplea reading of 6.4 which is below the normal range of 7.35 to 7.45 andthus indicates acidosis has likely occurred which affects (compromises)the vasculature structure.

In some embodiments, a pH level of 6.8 is used as the parameter tomodify the treatment modality. In other embodiments, the pH level of 6.4is used as the parameter to modify the treatment modality. By way ofexample, 6.8 could be a first predetermined level where if the measuredpH is at or below this level, the clinician would decide that blood clotremoval provides some risk and the method of clot removal needs to beassessed. By way of example, 6.8 could be the threshold for assessingthe type of treatment method and a pH level of 6.4 could be thepredetermined level where the clot should not be removed because of thecondition of the vasculature. In other embodiments, 6.0 could be thepredetermined level at which the clot would not be removed.

In some embodiments, a pH level of 6.8 is used as the parameter tomodify post treatment reperfusion. In other embodiments, the pH level of6.4 is used as the parameter to modify post treatment perfusion. By wayof example, 6.8 could be a first predetermined level where if themeasured pH is at or below this level, the clinician would decide thatblood flow restoration post blood clot removal is at risk and blood flowneeds to be controlled to gradually restore blood flow. By way ofanother example, 6.4 can be the threshold for assessing the treatmentmethod if the measured pH is at or below this level, the clinician woulddecide that blood flow restoration post blood clot removal is at riskand blood flow needs to be controlled to gradually restore blood flow.

In use, the catheter 10 (or 10′) can be inserted utilizing knownmethods, e.g., through a femoral approach or a brachial approach, andadvanced through the vascular system to the desired treatment site, e.g.a cerebral artery A. The catheter tip 11 is advanced past the blood clotC (see e.g., FIG. 5). The sensor is activated to measure pH, with the pHreader turned on so that pH value can be determined. As noted above, theclosed system advantageously enables the user to determine thevasculature condition by measuring the blood pH rather than the pH ofthe vasculature itself. Proper treatment approaches, e.g., decidingwhether the clot can be safely removed, selecting the safest clotremoval method or taking other precautions to protect the vessel, canthen be implemented. Also, restoration of blood flow can be controlledin accordance with the condition of the vessel.

FIGS. 6-8B illustrate an alternate embodiment for measuring pH utilizinga sensor on a guidewire instead of the catheter as in FIG. 1. In thisembodiment, guidewire 50 has a proximal portion 52 and a distal portion54. The guidewire 50 is sufficiently rigid to navigate the small vesselswhile having some rigidity to enable it to be directed around the curvesof the vasculature. In one embodiment the guidewire is hollow and thewire runs through the lumen from the sensor to the connector, and thewire, as in other embodiments herein, is preferably insulated. Inanother embodiment, the guidewire is a solid core and a polymeric jacketcontains the insulated wire on an outer surface of the guidewire. Theguidewire is illustrated within a lumen of a catheter 70 having a RHV 74attached to the proximal end. The RHV 74 is attached to the hub 72 ofthe catheter 70 and includes a side arm 75 for injection and/oraspiration. Coupler 80 is attached to the guidewire 50, and is connectedto cable 83 which is connected to pH reader 40. The pH reader can be thesame as in the embodiment of FIG. 1. In one embodiment, as shown in FIG.7, the coupler (connector) 80 is u-shaped with opening 81 between thelegs of the “u” dimensioned to frictionally clamp onto the outer wall ofthe guidewire 50. A two part connector as described above could also beutilized. Other methods of attachment are also contemplated includingmagnetic attachments for example. Cable 83 is connected to the coupler80 at one end 85 and connected at the opposing end 86 to reader 40.

The pH sensor 56 is positioned at a distal end of the guidewire 50 andis electrically coupled to coupler 80 and/or cable 84 via a pair ofwires (not shown) extending from the sensor 56. The wires can beembedded in a wall of the guidewire 50 or alternatively the guidewirecan have a lumen or channel through which the wires extend. In theembodiment of FIG. 8A, the sensor 56 is positioned on an outer wall ofthe guidewire 50, extending circumferentially around 360 degrees. Thesensor can also be incorporated into a marker band at the tip of theguidewire 50. In an alternate embodiment, the sensor 56′ and wires 57(only one is shown) of guidewire 50′ can be positioned inside theguidewire 50′, either internal of the inner wall of the guidewire asshown in FIG. 8B, or alternatively embedded in the wall of theguidewire. The catheter 70 through which the guidewire extends can havea marker band 79. Note in FIG. 8A, the catheter 70 and guidewire 50 arepositioned in a cerebral artery A distal of clot C.

In use, the switch 42 of the pH reader 40 is activated and the sensor 56is activated to measure the blood pH and the pH reader provides anumeric pH value of the blood. FIG. 6 shows a pH reading of 6.4 by wayof example. Note the guidewire 50 can be inserted utilizing knownmethods, e.g., through a femoral approach or a brachial approach, andadvanced through the vascular system to the desired treatment site, e.g.the cerebral artery. In one method, first an introducer is placed in thefemoral artery, and a large guidewire and guide catheter is advanced tothe carotid artery. The large guidewire is removed, and replaced with amicrocatheter 70 and a smaller dimensioned guidewire 50 of the presentinvention which contains sensor 56. The catheter tip 71 (containingmaker band 79 for imaging) and guidewire tip 51 are advanced past theblood clot C (see e.g., FIG. 8A). The sensor 56 measures the pH andtransmits the measurement through the wires extending in guidewire 50back to the cable 83 which in turn transmits it to the reader 40. Asnoted above, the closed system advantageously enables the user todetermine the vasculature condition by measuring the blood pH ratherthan the pH of the vasculature (or surrounding tissue) itself. Propertreatment approaches for the treating the blood clot can then be betterselected. That is, the physician can determine whether removal of theclot would be too traumatic to the vessel and risk hemorrhaging. Thephysician can also determine the safe restoration of blood flow andcontrol such blood flow in accordance with the condition of the vessel.Note the different parameters described above are applicable to thisembodiment (sensor on the guidewire) as well.

Note the sensors are shown at the distalmost tip of the catheter (FIGS.1-5) or guidewire (FIGS. 6-8B) but alternatively can be spaced proximalof the distalmost tip such as the sensor 56 a of guidewire 50 a of FIG.8C.

The pH sensors can be used in other applications such as in cases ofgangrene or tissue dying for some other reason to intravascularly assessthe vasculature or health of the tissue.

In an alternate embodiment, the oxygen level of the blood can bemeasured which is indicative of the oxygen and thus the health of thevasculature due to the closed or substantially closed system resultingfrom the blood clot. The system would be the same as with the abovedescribed systems, except one or more oxygen sensors (rather than pHsensors) would be provided on the catheter or the guidewire andconnected to an oxygen reader (meter) such as shown in FIG. 2B. Theoxygen reader provides an indicator of the oxygen level, by providingfor example a numeric value, or other indicator, to indicate a range oflow to high oxygen level measurements. The sensors can be positioned onthe catheter or guidewire in the similar manners of the pH sensorsdisclosed herein.

FIGS. 14A-14D illustrate one method of use of the present inventionillustratively showing the guidewire system of FIG. 6B. In this system,the health of the vasculature is assessed by measurement of the pH levelof the blood downstream of the clot so that a) a determination can bemade as to how the blood clot can be treated, including whether theblood clot should even be removed; and b) a determination can be made asto how blood flow should be restored if the blood clot is to be removed.

FIG. 14A shows a conventional introducer catheter 300 inserted throughthe femoral artery to provide access to the vascular system. Aconventional guide catheter 302 is inserted through the introducercatheter 300 and advanced through the vascular system to or adjacent thetargeted cerebral artery, e.g., advanced to the neck region of thepatient. The guidewire of the present invention, such as guidewire 50,is inserted through the guide catheter 302 and advanced adjacent theblood clot C as shown in FIG. 14B. (Note the coupler and reader are notshown in FIGS. 14B-14D) The guidewire 50 is then advanced past the clotC to a position downstream of the blood clot (occlusion). The pH levelof the blood downstream of the blood clot is measured by the pH sensoras described above (or alternatively by the oxygen sensor if an oxygensensor is utilized) and the reader provides a readout of the pH level.Based on this reading, the user is made aware of the pH level of thevessel downstream of the clot C, and thus the health of the vessel. Thisenables the user to determine, e.g., based on comparison to apredetermined pH level, if intravenous thrombolytic therapy, e.g.,injection of drugs to break up the clot, or mechanical thrombectomy tograsp and remove the clot is the better treatment method, or whetherremoval of the blood clot is too high risk and therefore should not beremoved. The reading also enables the user to determine the effect bloodflow will have on the vessel downstream of the clot once the blood clotis removed and blood flow is restored so the clinician can take steps tocontrol (regulate), e.g., slow, blood flow post clot removal.

FIG. 14C illustrates the next step of inserting a microcatheter 304 overthe guidewire 50. The microcatheter selected is based on the health ofthe vasculature. For example, in FIG. 14C, a mechanical treatment isselected and the microcatheter 304 having a mechanical thrombectomydevice 306 such as a stent-like device is inserted over the guidewire50. Note the mechanical thrombectomy device 306 has an expandable stentstructure which when expands captures clot which is removed as the stentis collapsed and withdrawn with the catheter. However, other mechanicalthrombectomy devices can be utilized such as motor controlled rotationalwires. In the method shown in FIG. 14C, the vasculature has beendetermined to have a low pH level, for example, below a pH level of 7,or another predetermined level such as in the examples discussed above,so the microcatheter selected also includes structure to provide slowreperfusion post clot treatment. More specifically, microcatheter 304has an inflation lumen 308 and an inflatable balloon 310 positioned at adistal end. The microcatheter 304 is advanced distal of the blood clot Cand the balloon 310 is inflated via inflation fluid through lumen 308prior to, during or after removal of the clot C as shown in FIG. 14C. Inthis manner, as the device 306 removes the clot C, the blood flow iscontrolled, i.e., full blood blow is not immediately restored. Theballoon 310 can be slowly and partially deflated to gradually restorefull blood flow as the pH level rises as determined by the continuedmeasurement of the pH level of the blood by the sensor of the guidewire50. With the pH level returned to a safe level, the balloon can bedeflated and the microcatheter 304 removed with blood flow fullyrestored. Note the guidewire 50 can be removed from within microcatheter304 prior to use of the device 306 to remove the blood clot so as not tointerfere with the device 306. It can periodically be reinserted withinmicrocatheter 304 to measure the pH level of the blood. In alternateembodiments, the guidewire 50 can be left in place within themicrocatheter so the sensor at the distal end can continuously orperiodically measure the blood pH. As can be appreciated, in thismethod, neither a guidewire nor catheter exchange is necessary. In somealternate embodiments, the microcatheter can include the pH sensor sothe guidewire could be removed and need not be reinserted for latermeasurement.

Although the balloon of FIG. 14C is shown distal of the blood clot, itis also contemplated that the balloon can be positioned on themicrocatheter proximal of the blood clot as in FIG. 14E. As shown, aballoon 311 can be positioned on microcatheter 304′ in addition to or inlieu of balloon 310 to control restoration of blood flow. Alternatively,the guide catheter can have a balloon at a distal end which isinflatable at a position proximal of the blood clot (FIG. 14F). Asshown, balloon 303 is positioned on guide catheter 302′ and can beprovided in addition to or in lieu of balloon 310 (and/or balloon 311).The balloons of these embodiments would block or reduce blood flow untilrestoration of full blood flow is desired. Thus, such balloons can beexpanded proximal and/or distal of the blood clot to control blood flow

In the alternate embodiment of FIG. 14D, the method of FIGS. 14A-14C isthe same except a microcatheter 312 different than microcatheter 306 isutilized when a determination is made, based on a pH level below apredetermined level, e.g., below a pH level of 7, or anotherpredetermined level such as the levels discussed above, that slowreperfusion during or after blood clot treatment (removal) is warranted.Microcatheter 312 has a lumen 314 for injection of cryogenic fluid.Injection of this cooling fluid cools slows the blood flow to provide analternate method of slowly restoring blood flow post clot removal. Theguidewire 50 can be removed from within microcatheter 312 prior to useif desired and periodically reinserted if desired, or alternatively leftin place as discussed above. The microcatheter can in an alternateembodiment include a pH sensor.

Note if an interventional therapy treatment is utilized, the catheter toinject the drugs for blood clot treatment can have a separate inflationlumen and an inflatable balloon to function to regulate blood flow inthe same manner as balloon 310 of microcatheter 304 or can have a lumen,either the same or different from the lumen to inject the drugs, toinject the cooling fluid to slowly restore blood flow in the same manneras microcatheter 312.

Note a comparison is made of the pH level to a predetermined level todetermine how to treat the clot. A comparison is also made of the pHlevel to a predetermined level to determine if slow reperfusion iswarranted. These predetermined levels can be the same or differentlevels.

Examples of such predetermined levels discussed above, as well as otherlevels, are fully applicable to these embodiments of FIGS. 14A-14F aswell.

Further note that the microcatheter can be inserted over the guidewirebefore or after pH level is measured. Also, in alternate embodiments theguide catheter can be provided with a mechanical thrombectomy device toremove the clot and/or a balloon or cooling fluid lumen so that aseparate catheter e.g. microcatheter 312, need not be utilized.

Also note that microcatheters 304 and 312 are examples of catheters thatcan be utilized to slow reperfusion, it being understood, that othercatheters with other structure to slow reperfusion are contemplated.Additionally, use of the balloon or cooling fluid disclosed herein canbe used on catheters other than catheters with the structure ofcatheters 304 and 312.

In the embodiment of FIG. 1 where a catheter rather than a guidewire isutilized to measure pH levels of blood, a microcatheter with a balloonor lumen for injection of cryogenic fluid can be utilized to slowlyrestore blood flow in the manner described above.

Note the aforedescribed sensors thereby provide a means for measuringthe blood pH which can be utilized to determine the health of thevasculature, the reader provides a means for indicating the sensed pH,the microcatheter provides a means for removing the clot and theinflatable balloon or cryogenic fluid provides a means for controllingthe rate of blood flow after clot removal.

Note the systems described above assess the blood distal of the bloodclot, however, it is also contemplated that assessment of the blood viapH measurement can be performed adjacent the blood clot but proximal tothe blood clot in the aforedescribed closed or substantially closedsystem. Such reading proximal the blood clot can also provide a readingof the vessel vitality adjacent the clot and therefore distal the clot.

Note the aforedescribed systems can alternatively measure oxygen levelof the blood rather than pH level as discussed above to determine thehealth of the vasculature and determine treatment as in FIGS. 14A-14D.

The systems are described herein mainly for use with treating bloodclots. However, any of the systems disclosed herein can also be used inother clinical applications. For example, one alternate application isto assess the condition of an organ, e.g., a transplanted organ such asa kidney, by measuring the pH of blood within the vasculature of theorgan to assess the condition of the organ. That is, an assessment of pHlevel in a vessel within the organ to assess vessel vitality willprovide an indication of the pH level of the organ to determine thevitality of the organ and whether steps need to be taken to address theorgan going bad or potentially not functioning properly.

Clot Determination

As noted above, the present disclosure provides a system to identify aparameter such as the composition of a clot in a vessel which willenable the physician to scientifically determine the clot makeup anddetermine the best course of treatment from the available tool sets.This can be achieved in accordance with one embodiment using ultrasound.

More specifically, in the embodiment utilizing ultrasonic waves, thedensity of the clot can be estimated, in vivo, by determining the timeit takes for an ultrasonic sound wave to “bounce” back from the clot.The longer the signal takes to return, the less dense the clot is. Thatis, an ultrasound signal will return more quickly when interacting witha denser substrate. The average densities of traditional “soft” clot ornormal clot and the denser fibrin clot is determined to providepredetermined parameters, and then the system of the present disclosurecompares the signal generated by the ultrasonic wave to these parametersto inform the physician of the type of clot. Thus, the system utilizes alogic circuit to determine the makeup of the clot quickly, efficientlyand effectively. By way of example, a soft clot can be assigned anumeral 1 and a hard clot assigned a numeral 10, and the clot densitymeasured to assign a value within this range so the physician wouldfirst be informed of the type of clot before taking treatment steps,such as removal of the clot. In other words, the measured averagedensities of both normal clot and fibrin will provide a “baseline”incorporated into the logic-circuit which will determine, in vivo duringthe surgical procedure, which clot type is present within the vessel.Other numeric values or indicators are also contemplated to indicatevarying densities.

To generate and provide a digital or analog readout of these ultrasoundsignals a piezoelectric signal transducer can be used. Piezoelectricmaterials are crystalline structures which undergo a mechanicaldeformation when a certain voltage is applied to the crystal. Thisproperty is used in conjunction with an applied AC voltage applied tothe crystal. As the AC voltage is applied to the piezo-material it willdeform and generate a sound wave. Likewise, when a mechanical load isplaced on the piezoelectric crystal a small voltage is generated. Thisproperty is used to convert an ultrasonic signal into a measurablevoltage. The piezoelectric crystal has a specific voltage/frequencyrelationship which can be used to convert between the two.

Because of these unique properties, the same piezoelectric transducerwhich generates an ultrasonic signal can also be used to receive thereflected signal returning from a substrate. Utilizing these propertiesthe ΔT (change in time) can be determined between the sent signal andthe received signal by having predetermined the average ΔT for bothnormal and fibrin clots; the designed logic circuit will be able todetermine which clot is present.

This ultrasonic signal is sent from within the vasculature to ensurethat interference from cranial tissues, muscle, bone, etc. do not affectmeasurements. The size and shape of the piezoelectric crystal willdetermine the distance at which the measurement can be best made.

Turning now to the system of FIGS. 9A-12B, a system for determining thetype of clot is illustrated, with FIG. 9 illustrating an embodimentwhere the density sensor (utilizing ultrasound as described above) is ona catheter and FIG. 11 illustrating an embodiment where the densitysensor (utilizing ultrasound) is on a guidewire. It is also contemplatedthat a density sensor can be positioned on the catheter and on theguidewire, and it is also contemplated that one or more density sensorscan be positioned on the catheter and one or more density sensorspositioned on the guidewire. This enables more than one region of theclot to be measured which could be beneficial in large clots.

Turning more specifically to the system of FIGS. 9A, 9B and 10, catheter110 has a proximal portion 112 and a distal portion 114. The cathetertube 116 is sufficiently flexible to navigate the small vessels whilehaving some rigidity to enable it to be directed around the curves ofthe vasculature. An RHV 120 is attached to the catheter hub 122 andincludes a side arm 124 for fluid injection and/or aspiration. Coupler130 is attached to the catheter 110, and is connected to cable 134 whichis connected to density reader (meter) 140. In one embodiment, thecoupler 130 can be the same as coupler 30 of the embodiment of FIG. 1and can be u-shaped with an opening between the legs of the “u”dimensioned to frictionally clamp onto the outer wall of the catheter110. That is, the coupler can be in the form of a U-shaped clip with theradius of the U smaller than that of the outer wall of the catheter soit flexes outwardly when placed over the strain relief of the catheterand then is frictionally retained on the catheter. In anotherembodiment, a second connector half is placed opposite the connector toform a 360 degree clip or clamp surrounding the outer wall of thecatheter to retain the connector (coupler) on the catheter 110. Othermethods of attachment are also contemplated such as magneticattachments. A cable 134 is connected to the coupler at one end 135 andconnected at the opposing end 136 to density reader 140. As shown, thecoupler 130 is attached to the region of catheter 110 just distal of hub122, although other locations are also contemplated.

The density sensor 126 is positioned at the distal portion 114 of thecatheter 110, at the distalmost tip 115 and is electrically coupled tocable 134 via a pair of wires (not shown) extending from the sensor 126to the coupler 130 and/or cable 134. The wires can be embedded in a wallof the catheter 110 or alternatively extend through a lumen in thecatheter 110. The sensor 126 in the illustrated embodiment is at thedistalmost tip but alternatively could be spaced from the distalmost endso the catheter tip can extend past the clot during use while the sensoris positioned within the clot. The sensor can be positioned on an outerwall of the catheter 110, extending circumferentially around 360degrees. The sensor can also be positioned inside the catheter 110,either internal of the inner catheter wall or alternatively embedded inthe wall of the catheter. Wires (not shown) connect the sensor to thecoupler 130 and/or cable 124.

The density reader 140 provides an indicator device and contains an onoff switch 142. A reading 144 provides a visual indication as a numericvalue representative of a comparative density as explained above. FIG.10 shows a density reading of “5” by way of example, indicating a clotdensity midway between the outer soft clot and outer hard clot range.Connector (coupler 120) is wired to the reader 140 which provides areading of the clot type based on the signal received from the sensor126 in response to the ultrasonic signal caused by the ultrasonic wavesapplied to the clot. In use, the catheter 110 can be inserted utilizingknown methods, e.g., through a femoral approach or a brachial approach,and advanced through the vascular system to the desired treatment site,e.g. the cerebral artery A. The catheter tip 115 is advanced past theblood clot C (see e.g., FIG. 9B) so the sensor 126 is located within theblood clot. The sensor 126 is activated, using ultrasonic waves tomeasure density, with the density reader providing a visual densityindication so the user can decide the optimal way to treat the clot.

FIG. 11A illustrates an alternate embodiment for measuring densityutilizing a sensor on a guidewire instead of the catheter as in FIG. 9A.In this embodiment, guidewire 150 has a proximal portion 152 and adistal portion 154. The guidewire 150 is sufficiently rigid to navigatethe small vessels while having some rigidity to enable it to be directedaround the curves of the vasculature. In one embodiment, the guidewireis hollow and the wires run through the lumen from the sensor to theconnector, and the wires are preferably insulated. In anotherembodiment, the guidewire is a solid core and a polymeric jacketcontains the insulated wires on an outer surface of the guidewire. Theguidewire is illustrated within a lumen of a catheter 170 having a RHV174 attached to the proximal end. The RHV 174 is attached to the hub 172of catheter 170 and includes a side arm 175 for injection and/oraspiration. Coupler 180 is attached to the guidewire 150, and isconnected to cable 183 which is connected to density reader 140. Thedensity reader 140 can be the same as in the embodiment of FIG. 10. Inone embodiment, the coupler is the same as coupler 80 of FIG. 7 and isu-shaped with an opening in the “u” dimensioned to frictionally clamponto the wall of the guidewire 150. A two part connector (coupler) asdescribed above can also be utilized. Other methods of attachment arealso contemplated such as magnetic attachments. Cable 183 is connectedto the coupler 180 at one end 185 and connected at the opposing end 186to meter 140.

Density sensor 156 is positioned at a distal end of the guidewire 150,either at the distalmost tip or spaced from the distalmost tip as shownin FIG. 11B, and is electrically coupled to coupler 180 and/or cable 184via a pair of wires (not shown) extending from the sensor 156. The wirescan be embedded in a wall of the guidewire 150 or alternatively theguidewire can have a lumen or channel through which the wires extend. Inthe embodiment of FIGS. 11A and 11B the sensor 156 is positioned on anouter wall of the guidewire 150, extending circumferentially around 360degrees. The sensor can also be incorporated into a marker band at thetip of the guidewire 150. In an alternate embodiment, the sensor can bepositioned inside the guidewire 150, either internal of the inner wallof the guidewire in the same manner as in the embodiment of FIG. 8B, oralternatively embedded in the wall of the guidewire. The catheter 170through which the guidewire extends can have a marker band. Note in FIG.11A, the guidewire 150 is positioned with the sensor in the clot C andthe catheter 170 is positioned in a cerebral artery A proximal of clotC.

In use, the density sensor 156 is activated to selectively measure thedensity of the blood clot and with switch 42 turned on, densityindication is provided. Note the guidewire 150 can be inserted utilizingknown methods, e.g., through a femoral approach or a brachial approach,and advanced through the vascular system to the desired treatment site,e.g. the cerebral artery. In a preferred method, first an introducer isplaced in the femoral artery, and a large guidewire and guide catheterare advanced to the carotid artery. The large guidewire is removed, andreplaced with a microcatheter 170 and a smaller dimensioned guidewire150 of the present invention which contains sensor 156. The catheter tip171 is advanced past the blood clot C. The guidewire 150 is positionedin the clot and in some embodiments the catheter 170 is withdrawnproximally to expose the sensor 156 within the clot C to measure thedensity of the clot and transmit the measurement through the wiresextending in guidewire 150 back to the cable 183 which in turn transmitsit to the reader 140. Proper treatment approaches for the treating theblood clot can then be better be selected. That is, the reader 140 isused to indicate density measurement so the physician can determine theoptimal way to treat the clot.

Combination of Systems

It is contemplated that the system for determining clot density (orother clot parameter) and the system for measuring the blood pH (orother blood parameter such as oxygen) can be used together. In suchsystem, both the density sensor and pH sensor (or oxygen sensor) alongwith a density and pH (or oxygen) reader are provided. Such system isshown in the embodiment of FIGS. 12A-13.

Catheter 210 has a proximal portion 212 and a distal portion 214. Thecatheter tube 216 is sufficiently flexible to navigate the small vesselswhile having some rigidity to enable it to be directed around the curvesof the vasculature. An RHV 220 is attached to the catheter hub 222 andincludes a side arm 224 for fluid injection and/or aspiration. Coupler230 is attached to the catheter 210, and is connected to cable 234 whichis connected to pH reader (meter) 241 of reader 240. Reader 240 providesboth a pH reading and a density reading. Although shown as a singlereader (meter), it is also contemplated that separate meters, such as inFIGS. 2 and 10 could be provided. In one embodiment, the coupler 230 isidentical to the embodiment of FIG. 4, being U-shaped with an opening inthe “u” dimensioned to frictionally clamp onto the outer wall of thecatheter 210. Alternatively, a second connector (coupler) half asdescribed above can be utilized. Other methods of attachment are alsocontemplated. Cable 234 is connected to the coupler 230 at one end 235and connected at the opposing end 236 to reader 241. As shown, thecoupler 230 is attached to the region of catheter 210 just distal of hub222, although other locations are also contemplated.

The pH sensor 226, identical to the sensor of FIG. 1, is positioned atthe distal portion 214 of the catheter 210 and is electrically coupledto cable 234 via a pair of wires (not shown) extending from the sensor226 to the coupler 230 and/or cable 234. The wires can be embedded in awall of the catheter 210 or alternatively extend through a lumen in thecatheter 210. In the embodiment of FIG. 12A, the sensor is positioned onan outer wall of the catheter 210, extending circumferentially around360 degrees in an identical manner as shown in FIG. 3A. The sensor canalso be incorporated into a marker band at the tip of the catheter 210.In the alternate embodiment, the sensor can be is positioned inside thecatheter 210 (similar to sensor 26′ of FIG. 3B), either internal of theinner catheter wall or alternatively embedded in the wall of thecatheter. The pH sensor can be positioned at the distalmost tip as shownor alternatively spaced proximally of the distalmost tip. Wires connectthe sensor 236 to the coupler 230 and/or cable 224.

The pH reader 241 contains an on off switch 248 to selectively provide areadout of the measured pH. A reading 244 provides a visual indication,as a numeric value, of the measured pH of the blood for the user todetermine the pH of the vasculature.

Guidewire 250 has a proximal portion 252 and a distal portion 254. Theguidewire 250 is sufficiently rigid to navigate the small vessels whilehaving some rigidity to enable it to be directed around the curves ofthe vasculature. The guidewire 250 is illustrated within a lumen ofcatheter 210. Coupler 280 is attached to the guidewire 250, and isconnected to cable 283 which is connected to density reader 245 ofreader 240. In one embodiment, the coupler 280 is the same as coupler 80of FIG. 7 and is u-shaped with opening in the “u” dimensioned tofrictionally clamp onto the wall of the guidewire 250. Alternatively, asecond connector (coupler) half as described above can be utilized.Other methods of attachment are also contemplated. Cable 283 isconnected to the coupler 280 at one end 285 and connected at theopposing end 286 to reader (meter) 245.

A density sensor 256, which is identical to sensor 156 of FIG. 11B, ispositioned at a distal portion of the guidewire 250, spaced proximallyof the distalmost tip, and is electrically coupled to coupler 280 and/orcable 283 via a pair of wires (not shown) extending from the sensor. Thewires can be embedded in a wall of the guidewire 250 or alternativelythe guidewire can have a lumen or channel through which the wiresextend. In the embodiment of FIG. 12A, the sensor 256 is positioned onan outer wall of the guidewire 250 in the same manner as sensor 156 ofFIG. 11B, extending circumferentially around 360 degrees. The sensor 256can also be incorporated into a marker band at the tip of the guidewire250. In an alternate embodiment, the sensor can be positioned inside theguidewire 250, either internal of the inner wall of the guidewire in thesame manner as shown in FIG. 8B, or alternatively embedded in the wallof the guidewire. The catheter 210 through which the guidewire 250extends can have a marker band. Note in FIG. 12A, the catheter 210 andguidewire 250 are positioned in a cerebral artery A distal of clot C. Inuse, the catheter 210 can be withdrawn with respect to the guidewire 250to expose the density sensor 256 within the clot as shown in FIG. 12Bwhere the density sensor 256 is proximal of the distal tip. In theembodiment wherein the density sensor 256 is at the distalmost tip, theguidewire 250 would be withdrawn further proximally until the distalmosttip (and sensor) is positioned in the clot.

In the embodiment where the pH sensor is on the guidewire (as in theembodiment of FIG. 6) and the density sensor is on the catheter (as inthe embodiment of FIG. 9A), the catheter need not be withdrawn. Thedensity sensor 256 can be positioned proximal of the pH sensor 226during use since the density sensor is exposed on the outside of thecatheter to measure the blood clot parameter and the pH sensor isexposed on the guidewire to measure the blood parameter downstream ofthe blood clot. In use, the density sensor is activated to measure clotdensity and switch 247 of the density reader 245 of reader 240 is turnedon to provide a visual numeric indication of a relative density. The pHsensor is activated either simultaneously, or at a different time, so pHreader 241 provides a visual numeric indication of blood pH.

It is also contemplated that in some embodiments a pH sensor (or oxygensensor) and a density sensor can both be positioned on a singleguidewire or a single catheter.

Note the guidewire 250 can be inserted utilizing known methods, e.g.,through a femoral approach or a brachial approach, and advanced throughthe vascular system to the desired treatment site, e.g., the cerebralartery. In one method, first an introducer would be placed in thefemoral artery, and a large guidewire and guide catheter would beadvanced to the carotid artery. The large guidewire is removed, andreplaced with a microcatheter 210 which contains a pH (or oxygen) sensor(or alternatively a density sensor), and a smaller dimensioned guidewire250 of the present invention which contains sensor 256. The catheter tip271 is advanced past the blood clot C. The sensor 256 of guidewire 250is positioned in the clot so the sensor measures the density of the clotand transmits the measurement through the wires extending in guidewire250 back to the cable 283 which in turn transmits it to the densityreader 245 of reader 240. (In the embodiment where the catheter containsthe density sensor, the guidewire can contain the pH (or oxygen) sensor.The pH sensor 226 is positioned distal (downstream) of the blood clot tomeasure pH of the blood distal of the clot and transmit it via wires tothe cable and pH reader 241. As noted above, the closed (orsubstantially closed) system advantageously enables the user todetermine the vasculature condition by measuring the blood pH ratherthan the pH of the vasculature (and surrounding tissue) itself. Propertreatment approaches for the treating the blood clot and/or restoring,i.e., controlling, blood flow can be better selected as discussed above.The density reading provides information on the blood clot itself. Asnoted above, an oxygen sensor can be used in the closed or substantiallyclosed system to determine the vasculature condition.

Note the couplers described herein are preferably coupled to thecatheter or guidewire prior to their insertion. However, alternatively,coupling can occur subsequent to insertion to facilitate maneuverabilityto the target site.

While the above description contains many specifics, those specificsshould not be construed as limitations on the scope of the disclosure,but merely as exemplifications of preferred embodiments thereof. Thoseskilled in the art will envision many other possible variations that arewithin the scope and spirit of the disclosure as defined by the claimsappended hereto.

What is claimed:
 1. A system for controlling reperfusion in a bloodvessel of a patient comprising: a flexible elongated member configuredand dimensioned for insertion in the vessel of the patient, theelongated member having a proximal portion and a distal portion, theelongated member configured for insertion so the distal portion extendsdistal of a clot in the blood vessel; a sensor positioned at the distalportion of the elongated member for positioning distal of the bloodclot, the sensor measuring a parameter of blood downstream of the clot;and an indicator communicating with the sensor, the indicator indicatinga measured parameter for insertion of an instrument for controllingblood flow.
 2. The system of claim 1, further comprising a connectorconnecting the elongated member to the indicator.
 3. The system of claim1, wherein the flexible elongated member comprises a guidewire.
 4. Thesystem of claim 1, wherein the sensor is embedded in a wall of theelongated member.
 5. The system of claim 1, wherein the sensor ispositioned on an outer surface of the elongated member.
 6. The system ofclaim 1, further comprising a catheter positionable over the flexiblemember, the catheter having a mechanical device for mechanicallyremoving the blood clot and a balloon distal of the mechanical device,the balloon inflatable to reduce blood flow in the vessel.
 7. The systemof claim 1, further comprising a catheter positionable over the flexiblemember, the catheter having a lumen to transport cryogenic fluid distalof the blood clot to reduce blood flow in the vessel.
 8. The system ofclaim 1, wherein the parameter is a pH level of blood, and the sensor isa pH sensor measuring the pH level of the blood downstream of the bloodclot to determine the condition of the vessel.
 9. The system of claim 8,wherein if the pH levels is below a predetermined level, blood flow rateis reduced after blood clot removal.
 10. The system of claim 1, whereinthe parameter is an oxygen level of blood, and the sensor is an oxygensensor measuring the oxygen level of the blood downstream of the bloodclot to determine the condition of the vessel.
 11. The system of claim10, wherein if the oxygen levels is below a predetermined level, bloodflow rate is reduced after blood clot removal.
 12. A method fordetermining the rate for reperfusion in a vessel of a patient comprisingthe steps of: a) providing an elongated flexible member; b) insertingthe flexible member through vasculature of the patient and past a clotin the vessel to a position downstream of the clot in the vessel; c)measuring a parameter of the blood downstream of the blood clot; and d)indicating to the user the parameter of the blood to enable the user todetermine a condition of the vasculature and determine a rate ofreperfusion.
 13. The method of claim 12, further comprising a pH sensoron a distal portion of the flexible member for measuring a pH level. 14.The method of claim 13, further comprising the step of inflating aballoon prior to removal of the blot clot to slow reperfusion if adetermination is made that slow perfusion is warranted.
 15. The methodof claim 14, further comprising the step of delivering a cryogenic fluidprior to removal of the blood clot to slow reperfusion if adetermination is made that slow perfusion is warranted.
 16. The methodof claim 14, wherein the step of inflating the balloon is performed ifthe indicator indicates the pH level is below
 7. 17. The method of claim13, wherein the flexible member is a guidewire, and further comprisingthe step of inserting a catheter over the guidewire, the catheter havingstructure to enable slow perfusion of blood after removal of the bloodclot.
 18. The method of claim 16, further comprising the step of slowingperfusion after removal of the blood clot by adjusting inflation of aninflatable balloon carried by the catheter.
 19. The method of claim 16,further comprising the step of slowing perfusion after removal of theblood clot by injecting a cryogenic fluid through the catheter.